18th International HIV Drug Resistance Workshop Basic Principles & Clinical Implications June 9–13 2009, Fort Myers, Florida, USA

SCREENING FOR HIV TROPISM USING POPULATION- BASED V3 GENOTYPIC ANALYSIS: A RETROSPECTIVE VIROLOGICAL OUTCOME ANALYSIS USING STORED PLASMA SCREENING SAMPLES FROM MOTIVATE-1

Antivir Ther 2009; 14 Suppl 1:A17 (abstract no. 15)

PR Harrigan¹, R McGovern¹, W Dong¹, A Thielen², M Jensen³, T Mo¹, D Chapman⁴, M Lewis⁵, I James⁵ and H Valdez^4
1BC Centre for Excellence in HIV/AIDS, Vancouver, Canada; ²Max-Planck Institute for Informatics, Saarbrucken, Germany; ³Fortinbras Research, Buford, GA, USA; ⁴Pfizer, Inc., New York, NY, USA; ⁵Pfizer Research and Development, Sandwich, UK

BACKGROUND: MOTIVATE-1 compared maraviroc+ optimised background versus placebo+OB in treatment- experienced patients with R5-HIV (standard Monogram Trofile). A subset screened without known R5-HIV entered a sister trial, A4001029. This study retrospectively examined population V3 loop sequence-based screening.

METHODS: Triplicate V3 loop sequencing performed on stored screening plasma samples was processed without human intervention using custom software (ReCall) blinded to clinical data. Tropism was inferred using either geno2pheno (g2P; 5% false-positive rate) or PSSM (-2.96 cutoff). Primary outcomes were concordance between the screening Trofile and genotype and viral load changes after starting maraviroc. 25% of the dataset was reserved for validation.

RESULTS: Preliminary genotypes and Trofile results were available from 1,230 samples (non-R5 n=553 by Trofile). Compared with Trofile, genotype had sensitivities of 63% and 56% and specificities of 91% and 90% for detecting non-R5 virus using g2P and PSSM, respectively. However, short-term viral load decreases were similar regardless of the assay used. For example, for patients screened as R5 by Trofile, median week 8 decreases were 2.4 logs (IQR 1.5→3) and 2.4 logs (IQR 1.2→3) in the MVC twice-daily and once-daily arms, respectively, compared with 2.5 logs (IQR 1.6→3) and 2.4 logs (IQR 1.2→3) for patients screened as R5 by g2P, and 2.5 logs (IQR 1.5→3) and 2.4 logs (IQR 1.1→3) for patients screened as R5 by PSSM. For patients screened as non-R5 by Trofile, decreases were 1.4 logs (IQR 0.2→3) and 0.6 logs (IQR 0→3) for MVC twice-daily and once-daily, respectively, compared with 1.5 logs (0.2→3) and 0.7 logs (0→3) for patients screened as non-R5 by g2P, and 1.2 logs (IQR 0.2→3) and 1.0 logs (IQR 0→3) for patients screened as non-R5 by PSSM. R5 groups had n>100 and all non-R5 groups had n>30. Median placebo week 8 viral load decreases were ≤1 log. Additional analyses are in progress to examine outcomes at 24 weeks and account for the activity of the OB regimen.

CONCLUSIONS: Despite apparently poor sensitivity of standard genotyping for predicting non-R5 HIV relative to standard Trofile, early virological reductions in this treatment-experienced population were similar regardless of the assay used.

2009-06-09
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